Cyclic peptides form a large class of natural and synthetic compounds. Naturally occurring cyclic peptides have diverse biological activities, e.g., antibiotics, toxins, hormones, and ion transport regulators. Naturally occurring cyclic peptides are not known to be synthesized via mRNA transcription, i.e., the amino acid sequence of naturally occurring cyclic peptides is not coded by the genome of the organism producing the material. Instead, the synthesis of naturally occurring cyclic peptides is dependent upon a series of non-transcriptional enzymes specifically dedicated to the synthesis of these products. Many cyclic peptides employ both amide and non-amide linkages and incorporate unnatural amino acids, i.e., amino acids not utilized in the mRNA transcriptional synthesis of linear proteins. Both D- and L-enantiomers of amino acids are widely employed in natural and synthetic amino acids synthetic analogs of several naturally occurring cyclic peptides have been designed and synthesized with modified biological activity.
Chemically, cyclic peptides are divided into two categories, i.e., homodetic peptides and heterodetic peptides. Homodetic peptides consist entirely of amino acid residues linked to one another by amide bonds. The present application is directed entirely to cyclic homodetic peptides. Heterodetic peptides include linkages other than amide linkages, e.g., disulfide linkages and ester linkages. Depsipeptides are a type of heterodetic peptide. Depsipeptides employ ester linkages. Valinomycin is a cyclic depsipeptide with an alternating chiral D-D-L-L-motif employing ester linkages within the ring. The present application specifically excludes heterodetic peptides. The chemistry of both homodetic and heterodetic cyclic peptides is extensively reviewed by Ovchinnikov et al. (1992), The Proteins, Vol. V: 307-642.
Molecular tubes are not previously known to be formed by cyclic peptides but are known to be formed by linear peptides. For example, gramicidin A is a linear pentadecapeptide having an alternating chiral D-L-motif. When integrated into a target bio-membrane, gramicidin A forms a left-handed anti-parallel double-stranded helix with 5.6-6.4 amino acid residues per turn. Gramicidin has an average outer diameter of approximately 16 Å and an average inner diameter of approximately 4.8 Å. The inner channel of gramicidin serves as a path for passive transmembrane ion transport. (See: Wallace, B. A. et al. (1988) Science, 44: 182-187; and Lang, D. (1988) Science, 44: 188-191.)
Molecular tubes may be formed from materials other that amino acids. Carbon tubes are disclosed by Iijima (Nature (1991), 354: 56-58) and Ebbesen et al. (Nature (1992), 358, 220-222). These carbon tubes are composed of graphite and have a concentric close ended structure. Inorganic tubes find wide application in chemistry, e.g., micro- and meso-porous inorganic solids known as zeolites are employed for enhancing a variety of reactions. The area of zeolites is reviewed by Meier et al., Atlas of Zeolite Structure Types, 2nd Edn (Butterworths, London, 1988).
What is needed is a method for assembling and disassembling molecular tubes of varying length and width using interchangeable subunits. What is needed is a versatile subunit for implementing the above method, i.e., a subunit which responds to a undergoes self-assembly and self-disassembly upon. What is needed is homodetic cyclic peptides which can be employed as subunits for self assembling and disassembling molecular tubes.